The wet epithelial surface of the eye is chemically, immunologically and as a result, ecologically unique and profoundly different from the keratinized surfaces of the surrounding adnexa. Although it is intuitively obvious that this would have a substantial impact on the microbes that inhabit and infect these distinct sites on the ocular landscape, we show in preliminary data that this has profound consequences for the types of methicillin resistant S. aureus (MRSA) that infect wet versus keratinized ocular epithelial tissues. The study of biogeography has been long established in zoology and botany, however only since genomics has given us the high?resolution power to view distinctions between microbes at various anatomical sites, has it been possible to study the biogeography of the human anatomy, including the eye and surrounding tissues ? and its impact on infectious diseases. We used this new biogeographical lens to view the ocular surface landscape, and in preliminary data showed for the first time, that a leading cause of multidrug resistant ocular infections at all anatomical sites, MRSA, specializes in infecting the ocular wet epithelial surface versus the keratinized epithelium of the adnexa. There is a critical gap in understanding why one MRSA lineage, CC5/USA100, is better positioned to infect the cornea and conjunctiva. As ocular surface infections are leading causes of vision loss worldwide, and CC5/USA100 MRSA represent the most highly antibiotic resistant MRSA clade, there is an urgency to understanding the drivers of MRSA biogeography for the eye. Achieving our aims will identify the precise host conditions under which selection for one MRSA lineage over another occurs, will identify the host factors contributing to this selection, and will identify the microbial factors that differentially empower CC5 strains to persist on the wet epithelium of the ocular surface as a forerunner to infection. The importance of this information is that it will provide new and critical insights that will allow eye care professionals to manage the ocular surface in a way that will reduce the likelihood of infection, by discovering biomarkers and key ocular surface defenses. Further, it will identify critical features of pathogenic MRSA lineages that now can be targeted therapeutically. Filling this critical knowledge gap will be a major advance for driving the field forward to mitigate an important global cause of vision loss.